Abstract
Most free-living organisms encode for a deoxyuridine triphosphate nucleotidohydrolase (dUTPase; EC 3.6.1.23). dUTPases represent a family of metalloenzymes that catalyze the hydrolysis of dUTP to dUMP and pyrophosphate, preventing dUTP from being incorporated into DNA by DNA polymerases, maintaining a low dUTP/dTTP pool ratio and providing a necessary precursor for dTTP biosynthesis. Thus, dUTPases are involved in maintaining genomic integrity by preventing the uracilation of DNA. Many DNA-containing viruses, which infect mammals also encode for a dUTPase. This review will summarize studies demonstrating that, in addition to their classical enzymatic activity, some dUTPases possess novel functions that modulate the host innate immune response.
Highlights
While there are some exceptions, most free-living organisms encode for a deoxyuridine triphosphate nucleotidohydrolase [1]
Deng et al [89] reported that of the fowl adenovirus (FAdV) serotypes examined, all contained a gene (ORF 1) that encodes for a deoxyuridine triphosphate nucleotidohydrolase (dUTPase) based upon the demonstration of the five conserved motifs characteristic of this protein
In a subsequent study [57], they reported that the Human endogenous retroviruses (HERVs)-K dUTPase exhibited a homotrimeric structure that was similar to the human dUTPase
Summary
While there are some exceptions, most free-living organisms encode for a deoxyuridine triphosphate nucleotidohydrolase (dUTPase; EC 3.6.1.23) [1]. Caprari et al [22] suggested that the dUTPases of double-stranded DNA viruses and retroviruses were obtained through different evolutionary events, but were acquired to serve the same function in different viral groups This assumption is based upon the premise that the only function of these dUTPase proteins is to enzymatically maintain genomic integrity. The monomeric dUTPases which exhibit an altered order series of conserved motifs (N-terminal to C-terminal; III, I, II, IV, and V) are reported to have evolved through a gene duplication event(s) This family of dUTPases are only observed in the Alpha- and Gammaherpesvirinae subfamilies of the Herpesvirales [18,20]. Except for members of the Alphaand Gammaherpesvinirae subfamilies, all these putative dUT genes encode for proteins that exhibit an ordered series of conserved motifs (N-terminal to C-terminal; I, II, III, IV, and V), which suggests a homotrimeric structure. Human cytomegalovirus NC_006273.2 Human herpesvirus 6A KP257584.1 Human herpesvirus 6B NC-000898.1 Human herpesvirus 7 NC_001716.2
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